Alzheimer's disease is a debilitating and deadly disease that subverts our most basic mental functions including the ability to think and to recall memories and eventually to even care for our own basic bodily needs. It is not only the most common form of dementia but also the sixth leading cause of death in the United States. As the elderly population grows, the prevalence of Alzheimer's disease will increase dramatically, presenting a pressing need in medicine and in our society. Since its identification a century ago, considerable progress has been made in understanding the symptoms and risk factors of Alzheimer's disease. However, our understanding of its molecular mechanisms is still very limited, and as a result there are no disease-modifying interventions to prevent or even delay its progression. I propose to develop new tools and combine biochemical, biophysical, and bioengineering approaches to determine the molecular basis of Alzheimer's disease. Both the tools and the scientific results will then be used to develop new prototype therapeutic agents. The technology developed for this goal will also have far-reaching impact on elucidating mechanisms for a variety of proteins.